Malaria is an infectious disease caused by Plasmodium falciparum, a protozoan parasite. In 2002, an estimated 2.2 million people were exposed to the threat of malaria with an estimate of 515 million clinical attacks, resulting in over a million deaths. Drug compounds derived from artemisinin have over a 90% efficacy rate as a therapeutic agent against malaria. For people in malaria-endemic countries, traditional first-line treatments, such as chloroquine, are no longer effective due to increasing drug resistance. Because of the development of these drug-resistant strains and low natural abundance, the demand for artemisinin has increased rapidly in the past decade. This proposal will seek to take full advantage of current literature precedent and apply this to enantio- and diastereoselective synthesis of artemisinin. Artemisinin is a sesquiterpene lactone that poses a synthetic challenge due to the stereochemically dense core containing seven stereocenters and an endoperoxide bridge. PUBLIC HEALTH RELEVANCE: The research plan involves investigating a peroxide exchange reaction in order to advance current methodology to improve upon the efficiency of current methods for isolating artemisinin. Successful realization of these goals will allow a rapid and efficient enatio- and diastereoselective synthesis and a novel strategy to solving problems of molecular complexity relevant to the target artemisinin.